Figure 3From: Obesity and diabetes cause cognitive dysfunction in the absence of accelerated β-amyloid deposition in a novel murine model of mixed or vascular dementia Aβ is not deposited in the vasculature. Large numbers of activated astrocytes could be seen both around amyloid cores and around some larger blood vessels (arrowheads) in older db/AD mice (a) There was no significant co-staining of amyloid and collagen IV, indicating that Aβ was not deposited in blood vessels. Red: GFAP, Green: Collagen IV, Blue: Amylo-Glo. db/AD mice did not have significantly more Aβ40 (b) or Aβ42 (c) in plasma, compared with AD mice (n = 18 F WT; 18 F db; 14 F AD; 13 F db/AD: 7–12 months old: p > 0.06), though mice containing the AD mutations had significantly more than those without (p ≤ 0.0001 for AD overall). Though the activities were significantly different in mice homozygous for the db mutation, neprilysin (d; p < 0.02) and insulin degrading enzyme (IDE: e; p < 0.003) activities were not increased relative to db WT mice (1–4 months old: n = 5 F/7 M Lepr +/+; 8 F/4 M Lepr db/db; 6 F/6 M Lepr db/+). Endothelin converting enzyme (ECE1: f) protein expression was unaffected by the db (p < 0.65) and AD (p > 0.1) genotypes (7–12 months old: n = 14 F/7 M WT; 16 F/5 M db; 12 F/5 M AD; 12 F/6 M db/AD). Similarly ECE1 (g) and ECE2 (not shown) mRNA expression was unchanged in diabetic mice (p > 0.38 for the db genotype overall), though ECE1 expression was reduced in AD mice relative to WT (* = p < 0.03: n = 1 F/4 M WT; 2 F/4 M db; 1 F/3 M AD; 1 F/3 M db/AD).Back to article page